PD-1/PD-L1抑制剂治疗肌层浸润性膀胱癌的研究进展

Research progress of PD-1/PD-L1 inhibitors in the treatment of muscle invasive bladder cancer

膀胱癌(bladder cancer)是我国老年男性最常见的泌尿系统恶性肿瘤之一,特别是肌层浸润性膀胱癌(MIBC)复发率高且预后差。在肿瘤局部进展或广泛转移导致无法实行根治性膀胱切除术时,以顺铂为基础的联合化疗往往被用作一线的治疗方案。近年来,多种免疫检查点抑制剂逐渐被研发并广泛应用于晚期膀胱癌的二线以及不能进行铂类化疗但免疫位点阳性患者的一线治疗。其中针对细胞程序性死亡分子1(PD-1)和细胞程序性死亡分子配体-1(PD-L1)的药物凭借其安全性和持久性展现出良好的应用前景,如美国食品药品监督管理局(FDA)批准的派姆单抗(Pembrolizumab)、纳武单抗(Nivolumab)以及国产的替雷利珠单抗(Tislelizumab)等,且与其他化疗药物和靶向药物联用时可起到协同作用并降低治疗无反应的发生率,本文就PD-1/PD-L1抑制剂的作用机制、局限性以及联合其他方案治疗肌层浸润性膀胱癌进行综述。

Bladder Cancer is one of the commonest urological malignancies in the elderly men in China,especially muscle invasive bladder cancer(MIBC)with high relapse rate and poor prognosis.Cisplatinbased combination chemotherapy is often used as the first-line treatment plan when local tumor progression or extensive metastasis makes radical cystectomy impossible.In recent years,a variety of immune checkpoint inhibitors have been gradually developed and widely used in the second-line treatment of advanced bladder cancer and the first-line treatment of patients who can’t undergo platinum chemotherapy but have positive immune sites.In them,drugs targeting programmed cell death molecule-1(PD-1)and programmed cell death molecule ligand-1(PD-L1)have shown good application prospects because of their safety and durability,such as Pembrolizumab and Nivolumab approved by U.S.Food and Drug Administration(FDA)and domestic Tislelizumab,etc.In addition,when combined with other chemotherapy drugs and targeted drugs,it can play a synergistic role and reduce the incidence of non-response to treatment.The mechanism of action and limitations of PD-1/PD-L1 inhibitors and their combined therapy with other schemes in the treatment of MIBC are reviewed in this paper.